Breast cancer is the second leading cancer death in women in the United States. Breast cancer mortality is primarily due to the occurrence of metastatic disease. Approximately 182,460 women in the United States are expected to be diagnosed with invasive breast cancer this year. Nearly 40,480 women died from breast cancer during the previous year. Presently there are about two and half million breast cancer survivors in the United States. The chance of a women having invasive breast cancer sometime during her life is about 1 in 8. The chance of dying from breast cancer is about 1 in 35. Breast cancer mortality is primarily due to the occurrence of metastatic disease. Because of high breast cancer mortality and toxicity of many current therapies, the identification of more effective therapies with fewer side effects and that specifically target metastasis are urgently needed. Research over the last three decades has provided convincing evidence supporting the premise that diets rich in fruits and vegetables may be protective against the risk of different types of cancer. Dietary agents can prevent carcinogenesis by different mechanisms including enhanced detoxification of the carcinogenic intermediates, inducing apoptosis in cancer but not normal cells, perturbing cell cycle progression and inhibiting angiogenesis and metastasis. Laboratory studies have shown strong chemopreventive and possibly cancer chemotherapeutic effects of whole foods and bioactive food components against cancers of skin, lung, breast, colon, liver, stomach, prostate and other sites (Kelloff, G. J. Perspective on cancer chemoprevention research and drug development. Adv. Cancer Res. 78: 199-334, 2000; Liu, R. H. Health benefits of fruit and vegetables and from additive and synergistic combinations of phytochemicals. Am. J. Clin. Nutr. 78: 517s-520s, 2003; Surh, Y. J. Cancer chemoprevention with dietary phytochemicals. Nat. Rev. Cancer 3:768-780, 2003; Milner, J. A. Molecular targets for bioactive food components. J. Nutr. 134: 2492s-2498s, 2004; Davis, C. D. and Milner, J. A. Diet and cancer prevention. In: Temple, N. J., Wilson, T. and Jacobs D. R. editors. Nutritional health: Strategies for disease prevention. Totowa N.J.: Humana Press. pp 151-171, 2006). Allium vegetable-derived diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) have strong anti-cancer properties. DAS has been shown to inhibit aberrant crypt foci (Wargovich, M. J. et al. Cancer Epidemiol. Biomarkers Prev. 5: 355-360, 1996), hepatic foci (Singh, A., Arora, A. and Shukla, Y. Modulation of altered hepatic foci induction by diallyl sulphide in Wistar rats. Eur. J. Cancer Prev. 13: 263-269, 2004) and N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumors in rats (Wargovich, M. J., Woods, C., Eng, V. W., Stephens, L. C. and Gary, K. Chemoprevention of N-nitrosomethylbenzylamine-induced esophageal cancer in rats by the naturally occurring thioether, diallyl sulfide. Cancer Res. 48: 6872-6875, 1988) and polycyclic aromatic hydrocarbon-induced skin carcinogenesis in mice (Singh, A. and Shukla, Y. Antitumor activity of diallyl sulfide on polycyclic aromatic hydrocarbon-induced mouse skin carcinogenesis. Cancer Lett. 131: 209-214, 1998). Oral gavage with DATS in male athymic mice significantly inhibited growth of PC-3 human prostate cancer xenografts (Xiao, D., Lew, K. L., Kim, Y. A., Zeng, Y., Hahm, E. R., Dhir, R. and Singh, S. V. Diallyl trisulfide suppresses growth of PC-3 human prostate cancer xenograft in vivo in association with Bax and Bak induction. Clin. Cancer Res. 12: 6836-6843, 2006). Berries (blackberry, raspberry, strawberry, etc) contain multiple bioactive compounds including polyphenols (such as several anthocyanins, ellagic acid, gallic acid etc), phytosterols, beta-carotene and alpha-carotene (Stone, G. D., Chen, T., Kresty, L. A., Aziz, R. M., Reinemann, T. and Nines, R. Protection against esophageal cancer in rodents with lyophilized berries: Potential mechanism. Nutr. Cancer 54: 33-46, 2006; Bravo, L. Polyphenols: Chemistry, dietary sources, metabolism and nutritional significance. Nutr. Rev. 56: 317-333, 1998). Dietary freeze-dried berries were shown to inhibit chemically-induced cancer of the rodent esophagus (Stone, G. D., Chen, T., Kresty, L. A., Aziz, R. M., Reinemann, T. and Nines, R. Protection against esophageal cancer in rodents with lyophilized berries: Potential mechanism. Nutr. Cancer 54: 33-46, 2006). Ellagic acid, one of the active components in berries, inhibits chemical carcinogenesis in lung (Boukharta, M., Jalbert, G. and Castonguay, A. Biodistribution of ellagic acid and dose-related inhibition of lung tumorigenesis in A/J mice. Nut. Cancer 18: 181-189, 1992; Mukhtar, H., Das, M., Del Tito, B. J. Jr. and Bickers, D. R. Protection against 3-methylcholanthrene-induced skin tumorigenesis in Balb/c mice by ellagic acid. Biochem. Biophys. Res. Commun. 119:751-757, 1984; Mandal, S. and Stoner, G. D. Inhibition of N-nitrosobenzylmethylamine-induced esophageal tumorigenesis in rats by ellagic acid. Carcinogenesis 11: 55-61, 1990). Research into food-derived bioactive components for cancer prevention is growing due to the relatively low or no toxicity detected and easy availability. Previous research has shown that the cooked mashed corm of the taro plant, known as poi, has antiproliferative activity against the rat YYT colon cancer cell line in vitro (Brown, A. C., Reitzenstein, J. E., Liu, J. and Jadus, M. R. The anti cancer effects of poi (Colocasia esculenta) on Colonic adenocarcinoma cells In Vitro. Phytother. Res.19: 767-771, 2005).
We have identified a therapeutic agent derived from edible roots of the plant Colocasia esculenta, commonly known as Taro, and from Xanthosoma sagittifolium, commonly known as Malanga Blanca and Yautia. We have shown for the first time that a water soluble extract of the taro (and Malanga Blanca and Yautia) corm (TE) has potent anti-metastatic activity. Using two highly metastatic, estrogen receptor, progesterone receptor and Her-2/neu negative murine mammary tumor cells (line 66.1 and 410.4) transplanted to immune competent syngeneic mice, we have shown that TE can significantly inhibit the lung colonizing ability of both cell lines and spontaneous metastasis of 66.1 cells. We have also shown that addition of TE to 3 of 7 human or murine cancer cell lines profoundly affects cellular morphology and inhibited proliferation in 6 of 9 cancer cell lines in a dose-dependent manner. We also show that TE has anticyclooxygenase activity by inhibiting expression of COX-2, and therefore also has therapeutic potential, for example, in the treatment of inflammatory conditions or diseases.